We plan to synthesize alternating polynucleotides with the structure (pG-pU)n with n up to 16. We have already prepared the appropriately protected G and U derivatives and are about to begin the synthesis of fully protected pGpU. We expect to prepare (pGpU)2 by chemical methods. Then we will evaluate enzymatic (RNA-ligase) and chemical methods for obtaining the higher oligomers. Once well-defined oligomers are available, we plan to use them as templates for the condensation of ImpApU. This should enable us to evaluate different catalysts for template-directed reactions in a well-defined chemical system that mimics fairly closely biological nucleic-acid replication and ligation. Another part of our effort will be concerned with metal-ion catalysis of polynucleotide formation from the 5'-phosphorimidazolides of the nucleotides. We have already shown that ImpG condenses very efficiently on a poly(C) template in the presence of 0.01M Pb2 plus ion, to give oligomers up to the 30-mer ion. The average molecular weight of the product is about 4000. We plan to extend this work to other nucleotides, and to other metals, particularly Zn2 plus. Since many of our products are 2' 5'-linked oligonucleotides, we plan to have them assayed for interferon induction.